title: The Cdc7 protein kinase is required for origin firing during S phase.
abstract: The Cdc7p protein kinase plays an essential, but undefined, role promoting S phase in the budding yeast, Saccharomyces cerevisiae. Previous experiments have shown that the essential function of Cdc7 is executed near the G1-S boundary; after Start but before the elongation phase of DNA replication. Origins of DNA replication fire throughout S phase in budding yeast. Therefore, the G1-S transition is a cell-cycle event that precedes, and is distinct from, the activation of individual origins. Consequently, we have asked whether Cdc7 is only required for S-phase entry or if it plays a role during S phase in origin firing. In this article, we show that partial loss of Cdc7 function results in slow progression through S phase rather than slow entry into S phase and that Cdc7 is still required for the timely completion of S phase after a block to elongation with hydroxyurea. This is because Cdc7 is still required for the activation of late-firing origins after the hydroxyurea block. These experiments show that, rather than acting as a global regulator of the G1-S transition, Cdc7 appears to play a more direct role in the firing of replication origins during S phase.
authors.affiliation: Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: K
authors.initials: K
authors.lastname: Bousset
authors.forename: J F
authors.initials: JF
authors.lastname: Diffley
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018983:DNA Footprinting; D004261:DNA Replication / Q000187:drug effects; D005434:Flow Cytometry; D016193:G1 Phase; D006918:Hydroxyurea / Q000494:pharmacology; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D018741:Replication Origin; D016196:S Phase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D018797:Cell Cycle Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C489404:CDC7 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D006918:Hydroxyurea